• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

基于亚细胞蛋白质组学和生物信息学分析鉴定胶质母细胞瘤替莫唑胺耐药相关的关键候选蛋白和通路。

Identification of Key Candidate Proteins and Pathways Associated with Temozolomide Resistance in Glioblastoma Based on Subcellular Proteomics and Bioinformatical Analysis.

机构信息

Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.

The Laboratory for Precision Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.

出版信息

Biomed Res Int. 2018 Mar 1;2018:5238760. doi: 10.1155/2018/5238760. eCollection 2018.

DOI:10.1155/2018/5238760
PMID:29687002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5852899/
Abstract

TMZ resistance remains one of the main reasons why treatment of glioblastoma (GBM) fails. In order to investigate the underlying proteins and pathways associated with TMZ resistance, we conducted a cytoplasmic proteome research of U87 cells treated with TMZ for 1 week, followed by differentially expressed proteins (DEPs) screening, KEGG pathway analysis, protein-protein interaction (PPI) network construction, and validation of key candidate proteins in TCGA dataset. A total of 161 DEPs including 65 upregulated proteins and 96 downregulated proteins were identified. Upregulated DEPs were mainly related to regulation in actin cytoskeleton, focal adhesion, and phagosome and PI3K-AKT signaling pathways which were consistent with our previous studies. Further, the most significant module consisted of 28 downregulated proteins that were filtered from the PPI network, and 9 proteins (DHX9, HNRNPR, RPL3, HNRNPA3, SF1, DDX5, EIF5B, BTF3, and RPL8) among them were identified as the key candidate proteins, which were significantly associated with prognosis of GBM patients and mainly involved in ribosome and spliceosome pathway. Taking the above into consideration, we firstly identified candidate proteins and pathways associated with TMZ resistance in GBM using proteomics and bioinformatic analysis, and these proteins could be potential biomarkers for prevention or prediction of TMZ resistance in the future.

摘要

替莫唑胺耐药性仍然是胶质母细胞瘤（GBM）治疗失败的主要原因之一。为了研究与替莫唑胺耐药相关的潜在蛋白和途径，我们对用替莫唑胺处理 1 周的 U87 细胞进行了细胞质蛋白质组学研究，随后进行了差异表达蛋白（DEPs）筛选、KEGG 途径分析、蛋白质-蛋白质相互作用（PPI）网络构建以及 TCGA 数据集关键候选蛋白的验证。共鉴定出 161 个 DEPs，包括 65 个上调蛋白和 96 个下调蛋白。上调的 DEPs 主要与肌动蛋白细胞骨架、黏附斑和吞噬体以及 PI3K-AKT 信号通路的调节有关，这与我们之前的研究一致。此外，从 PPI 网络中筛选出的由 28 个下调蛋白组成的最显著模块，其中 9 个蛋白（DHX9、HNRNPR、RPL3、HNRNPA3、SF1、DDX5、EIF5B、BTF3 和 RPL8）被鉴定为关键候选蛋白，它们与 GBM 患者的预后显著相关，主要涉及核糖体和剪接体途径。综上所述，我们首次使用蛋白质组学和生物信息学分析鉴定了与 GBM 中替莫唑胺耐药相关的候选蛋白和途径，这些蛋白可能是未来预防或预测替莫唑胺耐药的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/80506cc8d91e/BMRI2018-5238760.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/90b8c717dc33/BMRI2018-5238760.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/21d7ebab0c42/BMRI2018-5238760.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/7e89aa74c6ef/BMRI2018-5238760.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/56439a12c4af/BMRI2018-5238760.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/80506cc8d91e/BMRI2018-5238760.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/90b8c717dc33/BMRI2018-5238760.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/21d7ebab0c42/BMRI2018-5238760.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/7e89aa74c6ef/BMRI2018-5238760.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/56439a12c4af/BMRI2018-5238760.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72b3/5852899/80506cc8d91e/BMRI2018-5238760.005.jpg

相似文献

1
Identification of Key Candidate Proteins and Pathways Associated with Temozolomide Resistance in Glioblastoma Based on Subcellular Proteomics and Bioinformatical Analysis.基于亚细胞蛋白质组学和生物信息学分析鉴定胶质母细胞瘤替莫唑胺耐药相关的关键候选蛋白和通路。
Biomed Res Int. 2018 Mar 1;2018:5238760. doi: 10.1155/2018/5238760. eCollection 2018.
2
Downregulating DNA methyltransferase 3B by suppressing the PI3K/Akt signaling pathway enhances the chemosensitivity of glioblastoma to temozolomide.通过抑制 PI3K/Akt 信号通路下调 DNA 甲基转移酶 3B 可增强胶质母细胞瘤对替莫唑胺的化疗敏感性。
Mol Neurobiol. 2024 Sep;61(9):7066-7074. doi: 10.1007/s12035-024-04041-7. Epub 2024 Feb 17.
3
The E3 Ubiquitin Ligase NEDD4-1 Mediates Temozolomide-Resistant Glioblastoma through PTEN Attenuation and Redox Imbalance in Nrf2-HO-1 Axis.E3 泛素连接酶 NEDD4-1 通过 PTEN 衰减和 Nrf2-HO-1 轴中的氧化还原失衡介导替莫唑胺耐药性脑胶质瘤。
Int J Mol Sci. 2021 Sep 23;22(19):10247. doi: 10.3390/ijms221910247.
4
Sulforaphane reverses chemo-resistance to temozolomide in glioblastoma cells by NF-κB-dependent pathway downregulating MGMT expression.萝卜硫素通过NF-κB依赖性途径下调MGMT表达，逆转胶质母细胞瘤细胞对替莫唑胺的化疗耐药性。
Int J Oncol. 2016 Feb;48(2):559-68. doi: 10.3892/ijo.2015.3271. Epub 2015 Nov 27.
5
Sulforaphane enhances temozolomide-induced apoptosis because of down-regulation of miR-21 via Wnt/β-catenin signaling in glioblastoma.在胶质母细胞瘤中，萝卜硫素通过Wnt/β-连环蛋白信号通路下调miR-21，从而增强替莫唑胺诱导的细胞凋亡。
J Neurochem. 2015 Sep;134(5):811-8. doi: 10.1111/jnc.13174. Epub 2015 Jun 11.
6
Targeting miR-381-NEFL axis sensitizes glioblastoma cells to temozolomide by regulating stemness factors and multidrug resistance factors.靶向miR-381-NEFL轴通过调节干性因子和多药耐药因子使胶质母细胞瘤细胞对替莫唑胺敏感。
Oncotarget. 2015 Feb 20;6(5):3147-64. doi: 10.18632/oncotarget.3061.
7
Long-term in vitro treatment of human glioblastoma cells with temozolomide increases resistance in vivo through up-regulation of GLUT transporter and aldo-keto reductase enzyme AKR1C expression.长期体外使用替莫唑胺治疗人胶质母细胞瘤细胞可通过上调 GLUT 转运体和醛酮还原酶 AKR1C 表达增加体内耐药性。
Neoplasia. 2010 Sep;12(9):727-39. doi: 10.1593/neo.10526.
8
YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line.YKL-40表达下调是克服胶质母细胞瘤细胞系中替莫唑胺耐药性的关键因素。
Oncol Rep. 2014 Jul;32(1):159-66. doi: 10.3892/or.2014.3195. Epub 2014 May 16.
9
Up-regulation of MSH6 is associated with temozolomide resistance in human glioblastoma.MSH6的上调与人胶质母细胞瘤中替莫唑胺耐药相关。
Biochem Biophys Res Commun. 2018 Feb 19;496(4):1040-1046. doi: 10.1016/j.bbrc.2018.01.093. Epub 2018 Jan 31.
10
Up-Regulation of Cyclooxygenase-2 (COX-2) Expression by Temozolomide (TMZ) in Human Glioblastoma (GBM) Cell Lines.替莫唑胺（TMZ）上调人胶质母细胞瘤（GBM）细胞系中环氧化酶-2（COX-2）的表达。
Int J Mol Sci. 2022 Jan 28;23(3):1545. doi: 10.3390/ijms23031545.

引用本文的文献

1
Glioblastoma: Overview of Proteomic Investigations and Biobank Approaches for the Development of a Multidisciplinary Translational Network.胶质母细胞瘤：蛋白质组学研究及生物样本库方法概述，用于构建多学科转化网络
Cancers (Basel). 2025 Jun 26;17(13):2151. doi: 10.3390/cancers17132151.
2
Repurposing of CNS accumulating drugs Gemfibrozil and Doxylamine for enhanced sensitization of glioblastoma cells through modulation of autophagy.将中枢神经系统蓄积药物吉非贝齐和多西拉敏重新用于通过调节自噬增强胶质母细胞瘤细胞的敏感性。
Sci Rep. 2025 Jul 1;15(1):20560. doi: 10.1038/s41598-025-05054-5.
3
Identification and Verification of Key Genes Associated with Temozolomide Resistance in Glioblastoma Based on Comprehensive Bioinformatics Analysis.

本文引用的文献

1
Ribosomes are optimized for autocatalytic production.核糖体针对自身催化生产进行了优化。
Nature. 2017 Jul 19;547(7663):293-297. doi: 10.1038/nature22998.
2
The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity.哺乳动物核糖体相互作用组揭示了核糖体功能的多样性和异质性。
Cell. 2017 Jun 1;169(6):1051-1065.e18. doi: 10.1016/j.cell.2017.05.022.
3
DEAD-Box RNA Binding Protein DDX5: Not a Black-Box during Reprogramming.DEAD-Box RNA 结合蛋白 DDX5：在重编程过程中并非“黑箱”。
基于综合生物信息学分析的胶质母细胞瘤中与替莫唑胺耐药相关关键基因的鉴定与验证
Iran J Biotechnol. 2024 Oct 1;22(4):e3892. doi: 10.30498/ijb.2024.448826.3892. eCollection 2024 Oct.
4
Lavender Essential Oil and Its Terpenic Components Negatively Affect Tumor Properties in a Cell Model of Glioblastoma.薰衣草精油及其萜类成分对胶质母细胞瘤细胞模型中的肿瘤特性有负面影响。
Molecules. 2024 Dec 22;29(24):6044. doi: 10.3390/molecules29246044.
5
Proteomic Profiling of Pre- and Post-Surgery Saliva of Glioblastoma Patients: A Pilot Investigation.胶质母细胞瘤患者手术前后唾液的蛋白质组学分析：一项初步研究。
Int J Mol Sci. 2024 Dec 3;25(23):12984. doi: 10.3390/ijms252312984.
6
SPIN: sex-specific and pathway-based interpretable neural network for sexual dimorphism analysis.SPIN：基于性别特异性和通路的可解释神经网络，用于性别二态性分析。
Brief Bioinform. 2024 May 23;25(4). doi: 10.1093/bib/bbae239.
7
Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.小分子酪氨酸激酶抑制剂（TKIs）治疗脑胶质瘤。
Int J Mol Sci. 2024 Jan 23;25(3):1398. doi: 10.3390/ijms25031398.
8
Sleeping Beauty transposon mutagenesis in mouse intestinal organoids identifies genes involved in tumor progression and metastasis.小鼠肠道类器官中的睡美人转座子诱变鉴定出参与肿瘤进展和转移的基因。
Cancer Gene Ther. 2024 Apr;31(4):527-536. doi: 10.1038/s41417-023-00723-x. Epub 2024 Jan 4.
9
Antibody Profiling and In Silico Functional Analysis of Differentially Reactive Antibody Signatures of Glioblastomas and Meningiomas.抗体分析与差异反应性抗体标志物在脑胶质瘤和脑膜瘤中的计算机功能分析。
Int J Mol Sci. 2023 Jan 11;24(2):1411. doi: 10.3390/ijms24021411.
10
Preclinical and Clinical Applications of Metabolomics and Proteomics in Glioblastoma Research.代谢组学和蛋白质组学在胶质母细胞瘤研究中的临床前和临床应用。
Int J Mol Sci. 2022 Dec 25;24(1):348. doi: 10.3390/ijms24010348.
Cell Stem Cell. 2017 Apr 6;20(4):419-420. doi: 10.1016/j.stem.2017.03.006.
4
Role of uL3 in Multidrug Resistance in p53-Mutated Lung Cancer Cells.uL3在p53突变肺癌细胞多药耐药中的作用
Int J Mol Sci. 2017 Mar 3;18(3):547. doi: 10.3390/ijms18030547.
5
The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types.核糖体蛋白基因RPL5在多种癌症类型中是一种单倍剂量不足的肿瘤抑制基因。
Oncotarget. 2017 Feb 28;8(9):14462-14478. doi: 10.18632/oncotarget.14895.
6
Ribosomal Proteins Control or Bypass p53 during Nucleolar Stress.核糖体蛋白在核仁应激期间控制或绕过p53。
Int J Mol Sci. 2017 Jan 12;18(1):140. doi: 10.3390/ijms18010140.
7
Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans.剪接因子1调节秀丽隐杆线虫的饮食限制和TORC1途径寿命。
Nature. 2017 Jan 5;541(7635):102-106. doi: 10.1038/nature20789. Epub 2016 Dec 5.
8
Akt and β-catenin contribute to TMZ resistance and EMT of MGMT negative malignant glioma cell line.Akt和β-连环蛋白促成MGMT阴性恶性胶质瘤细胞系的替莫唑胺耐药性和上皮-间质转化。
J Neurol Sci. 2016 Aug 15;367:101-6. doi: 10.1016/j.jns.2016.05.054. Epub 2016 Jun 1.
9
Expression of dynein, cytoplasmic 2, heavy chain 1 (DHC2) associated with glioblastoma cell resistance to temozolomide.与胶质母细胞瘤细胞对替莫唑胺耐药相关的动力蛋白，细胞质 2，重链 1（DHC2）的表达。
Sci Rep. 2016 Jul 4;6:28948. doi: 10.1038/srep28948.
10
eIF1A/eIF5B interaction network and its functions in translation initiation complex assembly and remodeling.真核起始因子1A/真核起始因子5B相互作用网络及其在翻译起始复合物组装与重塑中的功能
Nucleic Acids Res. 2016 Sep 6;44(15):7441-56. doi: 10.1093/nar/gkw552. Epub 2016 Jun 20.